Current in vitro platforms are poor predictors of in vivo safety, efficacy and pharmacokinetics of therapeutic agents or therapeutic delivery systems having therapeutic agents owing to significant difference in the test conditions compared to physiological conditions. Traditional in vitro models routinely utilize 2D monolayers of cultured cells under static conditions for studying drug delivery and toxicity. These simplistic representations often result in waste metabolite buildup in the platform, which can provide misleading information on the physiological condition. In order to overcome this limitation, perfused cell culture systems or bioreactors were developed to continuously replenish the culture medium. However, the use of continuously fed system leads to cost prohibitive reagent volume requirements. Microfluidic bioreactors were developed to address this challenge, and offer several key advantages over conventional macro-physiological systems (e.g., hollow fiber or membrane-based technologies). For instance, microfluidic systems offer facile compatibility with co-culture conditions, in particular multi-cellular architectures, real-time optical monitoring, and a more accurate representation of cell-cell interactions. However, available biomicroreactors fail to capture key in vivo physiological features such as morphological size, physiological blood flow and cellular (biological) architecture of the specific organs being investigated. Therefore, there remains a need for improved cell culture devices in order to enable improved modeling of organ and/or physiological response to therapeutic agents or therapeutic delivery systems having therapeutic agents.
All aspects of the embodiments described in the figures can be used in conjunction with other embodiments in other figures. For example, posts can be used in a barrier layer or barrier conduit without being used in the central or interior chamber. Also, the figures are not to scale or dimension. For example, the distances between chambers may be different with respect to other distances between other chambers. While some aspects are shown to be symmetrical, those aspects may be asymmetrical.